The ability to reproduce is a gift generally taken for granted when all bodily functions perform properly and the ability to conceive is high.
For many couples one or the other or both may have conditions that reduce or limit this ability to reproduce.
For this group of people medical treatments to increase the potential for having a child include fertility drugs, surgery, artificial insemination, in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), zygote intrafallopian transfer (ZIFT), intracytoplasmic speron injection (ICSI), donor eggs and embryos and gestational carriers (also known as surrogate mothers).
Each of these treatments has certain risks associated with the benefits. One of the more certain risks is the cost to conceive becomes more expensive based on the difficulty and technical complexity of the procedure.
Even the lower cost use of fertility drugs has some very high risk factors. In U.S. Pat. No. 6,879,713 some of the costs are recited. “Multiple gestations are increasing at an alarming rate due to the growing use of infertility treatments. Presently, 77% of triplets result from assisted reproduction technologies (ART's). Between 1980 and 1994, 10% of the 37,514 triplets, quadruplets, and other-higher multiplies died in their first year, according to the National Center for Health Statistics (Belluck, 1998). Multiple pregnancies suffer a five fold higher stillbirth rate than singleton pregnancies. Of those that survive, 92% are born prematurely and below normal birth weight, which can lead to health and developmental problems. Triplets are twice as likely to develop blindness, mental retardation or seizure disorders as singletons (Belluck, 1998). The rate of cerebral palsy in multiple gestation is 12 times that of singleton pregnancies (Crether, 1993). In a study of 13,206 pregnancies at a Boston hospital, the average cost for postpartum care of triplets was $109,000 (Callahan, 1994).”
This prior art patent was directed to improving the success rate of in vitro fertilization (IVF) of the patient while reducing the risk of multiple births.
During in vitro fertilization (IVF), eggs or oocytes removed from the ovaries are fertilized with sperm (from a partner or a donor) in a laboratory. The resulting embryos are placed in the patient's uterus. The woman may need to take fertility drugs before the procedure, which will raise her risk of having multiple births and of developing ovarian hyperstimulation syndrome (OHSS). Success rates range between 28 and 35 percent of women who try in vitro fertilization conceive. This procedure usually costs between $8,000 and $15,000.
Understanding the basic mechanisms that control the natural selection of the relatively few oocytes that are ovulated, can provide the key to tapping this enormous genetic resource. Applied to women, this knowledge will produce new insights into causes of ovarian dysfunction, and can possibly lead to improved procedures for the diagnosis of infertility, and reduce the risk of high multiple gestations generated by empiric infertility therapies.
A previous study (Battaglia, 1996) compared spindles of oocytes from two groups of women, aged 20 to 25, and aged 40 to 45 years using immunofluorescence and high-resolution, confocal microscopy, and found that meiotic spindles from older women exhibited significantly more abnormalities in chromosome placement and structure. In the older group, 79% of oocytes from the older group exhibited abnormal spindle structure, including abnormal tubulin placement and displacement of one or more chromosomes from the metaphase plate. In the younger group, only 17% exhibited such abnormalities. Spindles in the younger group appeared well ordered, and held chromosomes aligned on the metaphase plate. This data suggests that the architecture of the meiotic spindle is altered in older women, possibly explaining their higher prevalence of aneuploidy.
Most clinical embryo viability scoring systems currently used in IVF laboratories focus on embryo morphology. However, because the oocyte serves as the “stem cell” for the embryo, and because more than 80% of aneuploidies that appear in preimplantation embryos originate in the oocyte spindle structure, the evaluation of oocyte structure and determination of fertilization and developmental potential is important, and examination of an important structure in oocytes, the meiotic spindle, is key.
Accordingly, U.S. Pat. No. 6,874,713 relates to a new method of imaging the translucent oocyte cells which is non-invasive.
While this is no doubt helpful it provides no good treatment technique for superior oocyte production in older women or those with an infertility issue.
Haifan Lin of Duke University in U.S. Pat. No. 6,723,534 discloses an important finding with regard to gene therapy wherein Lin purified and isolated PIWI family of genes and gene products. This PIWI family of gene products is characterized as having activity in the growth, proliferation and self renewing division of stem cells and proliferation of primordial germ cells. Dr. Lin's recitation of the current state of the art as to our understanding of stem cell stimulation and extrinsic signaling is noted as follows:                Stem cells are a very small number of founder cells that play a central role in tissue development and maintenance. In human bodies, stem cells are responsible for generating and/or maintaining approximately 90% of cells in the adult tissues. Over-proliferation of malignant stem cells is the leading cause of cancer while under-proliferation of stem cells or stem-like progenitor cells leads to tissue dystrophy, anemia, immunodeficiency, and male infertility. The crucial role of stem cells has long been attributed to their ability to self-renew and to generate immense number of specialized cells on demand.        The ability of stem cells to self-renew and to produce a large number of differentiated progeny is critical for the development and maintenance of a wide variety of tissues in organisms ranging from insects to mammals (reviewed in Potten, 1997; Lin, 1997; Lin and Schagat, 1997; Morrison et al., 1997). This self-renewing ability is controlled both by extrinsic signaling and by cell-autonomous mechanisms (reviewed in Morrison et al., 1997; Lin and Schagat, 1997). Cell autonomous mechanisms have been elucidated in a few stem cell models such as neuroblasts and germline stem cells in Drosophila (Lin and Schagat, 1997; Deng and Lin, 1997), whereas the role of extrinsic signaling has been elucidated in several systems. For example, the proliferation and differentiation of mammalian stem cells in the hematopoietic, epidermal, and nervous systems depend on extrinsic signals that act on specific receptors on the stem cell surface (Morrison et al., 1997).        In diverse organisms ranging from invertebrates to mammals, the proliferation of germ cells, some of which possess stem cell properties, has been postulated, and, in some cases, shown to be regulated by neighboring non-mitotic somatic cells (Lin, 1997). Particularly, in C. elegans, cell—cell interactions between the somatic distal tip cell (DTC) at the end of each gonadal arm and the underlying mitotic germline nuclei via the lag-21g/p-1 signaling pathway provides a paradigm for soma-germline interaction (reviewed in Kimble and Simpson, 1997). The glp-1 pathway is required to maintain a population of mitotically active nuclei in the germline.        However, few molecules and/or mechanisms identified in a particular type of stem cells have been shown to be applicable to other stem cell systems. For example, the glp-1 equivalent pathway in Drosophila does not play a role in regulating GSC division and maintenance (Ruohala et al., 1991; Xu et al., 1992).        The self-renewing asymmetric division of GSCs in the Drosophila ovary is known to be controlled both by an intracellular mechanism (Deng and Lin, 1997) and by cell-cell interactions (Lin and Spradling, 1993). The intracellular mechanism involves a cytoplasmic organelle termed the spectrosome that controls the orientation of GSC division (Lin et al., 1994; Deng and Lin, 1997). The cell—cell interaction mechanism involves terminal filament cells, as shown by laser ablation studies (Lin and Spradling, 1993). Recently, dpp has been shown as a key signaling molecule required for GSC division and maintenance (Xie and Spradling, 1998). It is possible that the dpp signal emanates from somatic cells. Alternatively, dpp signal may originate from the germline or even within GSCs, like its mammalian homologs (Zhao et al., 1996).        In mammals, primordial germ cells cultured from the genital ridge have the ability to give rise to pluripotent embryonic stem cells. For example, U.S. Pat. No. 5,690,926 issued Nov. 25, 1997 to Hogan; U.S. Pat. No. 5,670,372 issued Sep. 23, 1997 to Hogan; and U.S. Pat. No. 5,537,357 issued Sep. 26, 1995 to Hogan each disclose pluripotential mammalian embryonic stem cells and methods of making the same. The disclosure of these patents is limited to mammalian embryonic stem cells and particularly to the culturing of murine and other mammalian embryonic stem cells using a combination of growth factors consisting of SCF, FGF and LIF.        Current prior art reports on the culture of avian primordial germ cells (PGCs) have concentrated on efforts to maintain a PGC-phenotype and to stimulate proliferation. See e.g., Chang, I. K. et al., Cell. Biol. Int. 1997 Aug. 21(8): 495-9; Chang, I. K. et al., Cell. Biol. Int. 1995 Feb. 19(2): 143-9; Allioli, N. et al., Dev. Biol. 1994 September; 165(1): 30-7 and PCT Publication No. WO 99/06533, published Feb. 11, 1999 (Applicant—University of Massachusetts; Inventors—Ponce de Leon et al.).        As illustrated above, numerous attempts have been devoted to identify genes that control the self-renewing ability of stem cells or the proliferation of primordial germ cells. As a result, a number of growth factors and signaling molecules, such as Steel factor and its c-kit receptor, have been identified to regulate such activity in certain tissues. Despite this progress, there remains a long-felt and continuing need to identify genes that play a role in modulating the growth and self-renewing division of stem cells, particularly GSCs, and that play a role in modulating proliferation of primordial germ cells.        
Dr. Lin's work is promising in the area of a males reproductive organs sperm generating capability. Similarly new techniques using genes differentially expressed in secretory versus proliferative endometrium can be used to diagnose disease, identify physiological state, design drugs and monitor therapies are taught in U.S. Pat. No. 6,884,578. This patent is particularly useful in uncovering some major insights into the complexity of the female reproductive tissues and organs.
The present invention offers a new technique to enhance the reproductive potential of both males and females.
One objective of the present invention is to assist in regeneration of the male or female reproductive tissues and organs to correct at least partially degenerative conditions resulting form aging or disease.
Another objective of the present invention is to stimulate the healing process of the male or female reproductive system after corrective surgery in cases where surgery is required to repair a defect in reproductive tissue or organs.
Another objective is to stimulate tissue revascularization and blood flow effectively to improve either performance or sensitivity to sexual contact thereby enhancing sexual experience for either a male or female.
These and other objectives are achieved using the inventive technology described herein.